The present invention relates to novel heterocyclic compounds and to their formulation and use as pharmaceuticals.
The modes of action of phosphodiesterases and also tumour necrosis factor (TNF), and the therapeutic utilities of inhibitors thereof, are described in WO-A-97/4433 7 and U.S. Pat. Nos. 5,925,636 and 5,972,936, the contents of which are incorporated herein by reference. These reference describe benzofurans having such activity.
This invention provides novel compounds having therapeutic utility, in particular for the treatment of disease states associated with proteins which mediate cellular activity, for example by inhibiting TNF and/or PDE IV. According to the invention, the compounds are of formula (i): 
wherein R1 is C1-3 alkyl optionally substituted with one or more fluorines;
R2 is CH2OCH3 or 2 or 3-tetrahydrofuranyl,
R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) 
R4 is C1-3 alkyl and
R5 and R6, which may be the same or different, each represents C,1-3 alkyl, halogen, CF3 or CN
or a pharmaceutically-acceptable salt thereof
In summary, the compounds of the invention represent a selection within the scope of WO-A-97/44337. The novel compounds have superior in vivo activity.
This invention provides also a method for mediating or inhibiting the enzymatic activity or catalytic activity of PDE IV in a mammal in need thereof and for inhibiting the production of TNF in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of Formula (i) or a pharmaceutically-acceptable salt thereof